WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202130
CAS#: 1070409-31-2 (tris salt)
Description: Palifosfamide, also known as ZIO201, is a synthetic mustard compound with potential antineoplastic activity. An active metabolite of ifosfamide covalently linked to the amino acid lysine for stability, palifosfamide irreversibly alkylates and cross-links DNA through GC base pairs, resulting in irreparable 7-atom inter-strand cross-links; inhibition of DNA replication and cell death follow. Unlike ifosfamide, this agent is not metabolized to acrolein or chloroacetaldehyde, metabolites associated with bladder and CNS toxicities. In addition, because palifosfamide does not require activation by aldehyde dehydrogenase, it may overcome the tumor resistance seen with ifosfamide.
MedKoo Cat#: 202130
CAS#: 1070409-31-2 (tris salt)
Chemical Formula: C8H22Cl2N3O5P
Molecular Weight: 342.15
Elemental Analysis: C, 28.08; H, 6.48; Cl, 20.72; N, 12.28; O, 23.38; P, 9.05
Related CAS #: 1070409-31-2 (tris salt); 31645-39-3 (free acid)
Synonym: ZIO201; ZIO-201; ZIO 201; IPAM; NSC 297900; NSC-297900; NSC297900; isophosphoramide mustard; Palifosfamide. Palifosfamide tris salt; Trade name: Zymafos.
IUPAC/Chemical Name: N,N'-Bis(2-chloroethyl)phosphorodiamidic acid
InChi Key: BKCJZNIZRWYHBN-UHFFFAOYSA-N
InChi Code: InChI=1S/C4H11Cl2N2O2P/c5-1-3-7-11(9,10)8-4-2-6/h1-4H2,(H3,7,8,9,10)
SMILES Code: O=P(NCCCl)(NCCCl)O.NC(CO)(CO)CO
Palifosfamide (ZIO-201) is currently developed by ZIOPHARM Oncology, Inc. It is a proprietary stabilized metabolite of ifosfamide. Ifosfamide has been shown to be effective in high doses in treating testicular cancer, sarcoma and lymphoma. Ifosfamide-based treatment generally represents the standard of care for sarcoma; however, it is not approved by the FDA in this indication. Ifosfamide metabolites include acrolein and chloroacetaldehyde, both highly toxic. Preclinical studies have shown that palifosfamide has activity in leukemia and solid tumor cancers. These studies also indicate that palifosfamide has a better safety profile than ifosfamide, likely because the toxic metabolites of ifosfamide, acrolein and chloroacetaldehyde are not present in palifosfamide. We believe the administration of palifosfamide may avoid many of the toxicities of ifosfamide without compromising the activity of the drug. see ZIOPHARM's website: http://www.ziopharm.com/clinical_zio201.php.
1: Williams R. Discontinued in 2013: oncology drugs. Expert Opin Investig Drugs. 2015 Jan;24(1):95-110. Epub 2014 Oct 14. PubMed PMID: 25315907.
2: Movva S, Verschraegen C. Systemic management strategies for metastatic soft tissue sarcoma. Drugs. 2011 Nov 12;71(16):2115-29. doi: 10.2165/11594500-000000000-00000. Review. PubMed PMID: 22035513.
3: Jones B, Komarnitsky P, Miller GT, Amedio J, Wallner BP. Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin. Anticancer Drugs. 2012 Feb;23(2):173-84. doi: 10.1097/CAD.0b013e32834d73a6. PubMed PMID: 22027537.
4: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Dec;31(10):661-700. PubMed PMID: 20140276.
5: Jung S, Kasper B. Palifosfamide, a bifunctional alkylator for the treatment of sarcomas. IDrugs. 2010 Jan;13(1):38-48. Review. PubMed PMID: 20024846.
6: Hingorani P, Zhang W, Piperdi S, Pressman L, Lin J, Gorlick R, Kolb EA. Preclinical activity of palifosfamide lysine (ZIO-201) in pediatric sarcomas including oxazaphosphorine-resistant osteosarcoma. Cancer Chemother Pharmacol. 2009 Sep;64(4):733-40. doi: 10.1007/s00280-008-0922-4. Epub 2009 Feb 18. PubMed PMID: 19224214.
7: Anderson P, Aguilera D, Pearson M, Woo S. Outpatient chemotherapy plus radiotherapy in sarcomas: improving cancer control with radiosensitizing agents. Cancer Control. 2008 Jan;15(1):38-46. Review. PubMed PMID: 18094659.